Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

James N. Ingle; Dongsheng Tu; Joseph L. Pater; Silvana Martino; Nicholas J. Robert; Hyman B. Muss; Martine J. Piccart; Monica Castiglione; Lois E. Shepherd; Kathleen I. Pritchard; Robert B. Livingston; Nancy E. Davidson; Larry Norton; Edith A. Perez; Jeffrey S. Abrams; David A. Cameron; Michael J. Palmer; Paul E. Goss

doi:10.1007/s10549-006-9207-y

Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

James N. Ingle, Dongsheng Tu, Joseph L. Pater, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Lois E. Shepherd, Kathleen I. Pritchard, Robert B. Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, David A. Cameron, Michael J. Palmer, Paul E. Goss

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77 Scopus citations

Abstract

Purpose. MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.

Original language	English (US)
Pages (from-to)	295-300
Number of pages	6
Journal	Breast Cancer Research and Treatment
Volume	99
Issue number	3
DOIs	https://doi.org/10.1007/s10549-006-9207-y
State	Published - Oct 2006

Keywords

Adjuvant hormonal therapy
Early breast cancer

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1007/s10549-006-9207-y

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Ingle, J. N., Tu, D., Pater, J. L., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Shepherd, L. E., Pritchard, K. I., Livingston, R. B., Davidson, N. E., Norton, L., Perez, E. A., Abrams, J. S., Cameron, D. A., Palmer, M. J., & Goss, P. E. (2006). Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial. Breast Cancer Research and Treatment, 99(3), 295-300. https://doi.org/10.1007/s10549-006-9207-y

Ingle, JN, Tu, D, Pater, JL, Martino, S, Robert, NJ, Muss, HB, Piccart, MJ, Castiglione, M, Shepherd, LE, Pritchard, KI, Livingston, RB, Davidson, NE, Norton, L, Perez, EA, Abrams, JS, Cameron, DA, Palmer, MJ & Goss, PE 2006, 'Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial', Breast Cancer Research and Treatment, vol. 99, no. 3, pp. 295-300. https://doi.org/10.1007/s10549-006-9207-y

@article{fc12e1b744eb45bc91c2887998b7972d,

title = "Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial",

abstract = "Purpose. MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.",

keywords = "Adjuvant hormonal therapy, Early breast cancer",

author = "Ingle, {James N.} and Dongsheng Tu and Pater, {Joseph L.} and Silvana Martino and Robert, {Nicholas J.} and Muss, {Hyman B.} and Piccart, {Martine J.} and Monica Castiglione and Shepherd, {Lois E.} and Pritchard, {Kathleen I.} and Livingston, {Robert B.} and Davidson, {Nancy E.} and Larry Norton and Perez, {Edith A.} and Abrams, {Jeffrey S.} and Cameron, {David A.} and Palmer, {Michael J.} and Goss, {Paul E.}",

note = "Funding Information: We are indebted to the women who participated in this study; to the trial committee; to the investigators, clinical research associates, and pharmacists from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the Cancer and Leukemia Group B, the North Central Cancer Treatment Group, the European Organization for Research and Treatment of Cancer, the International Breast Cancer Study Group, and centers in England including the Royal Marsden, St. George{\textquoteright}s, and the Withington Hospitals; to the members of the Data Safety Monitoring Committee; and to the central office staff of the NCIC CTG who contributed to the conduct of the trial. The MA.17 study was supported by the Canadian Cancer Society through National Cancer Institute of Canada Grant 10362, grants from the National Cancer Institute of the United States (CA31946, CA21115, CA25224, CA38926 and CA32102), and Novartis Pharmaceuticals.",

year = "2006",

month = oct,

doi = "10.1007/s10549-006-9207-y",

language = "English (US)",

volume = "99",

pages = "295--300",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer New York",

number = "3",

}

TY - JOUR

T1 - Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

AU - Ingle, James N.

AU - Tu, Dongsheng

AU - Pater, Joseph L.

AU - Martino, Silvana

AU - Robert, Nicholas J.

AU - Muss, Hyman B.

AU - Piccart, Martine J.

AU - Castiglione, Monica

AU - Shepherd, Lois E.

AU - Pritchard, Kathleen I.

AU - Livingston, Robert B.

AU - Davidson, Nancy E.

AU - Norton, Larry

AU - Perez, Edith A.

AU - Abrams, Jeffrey S.

AU - Cameron, David A.

AU - Palmer, Michael J.

AU - Goss, Paul E.

N1 - Funding Information: We are indebted to the women who participated in this study; to the trial committee; to the investigators, clinical research associates, and pharmacists from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the Cancer and Leukemia Group B, the North Central Cancer Treatment Group, the European Organization for Research and Treatment of Cancer, the International Breast Cancer Study Group, and centers in England including the Royal Marsden, St. George’s, and the Withington Hospitals; to the members of the Data Safety Monitoring Committee; and to the central office staff of the NCIC CTG who contributed to the conduct of the trial. The MA.17 study was supported by the Canadian Cancer Society through National Cancer Institute of Canada Grant 10362, grants from the National Cancer Institute of the United States (CA31946, CA21115, CA25224, CA38926 and CA32102), and Novartis Pharmaceuticals.

PY - 2006/10

Y1 - 2006/10

N2 - Purpose. MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.

AB - Purpose. MA.17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA.17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole, with the trend being significant (p<0.0001 and p=0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p=0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p=0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting.

KW - Adjuvant hormonal therapy

KW - Early breast cancer

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UR - http://www.scopus.com/inward/citedby.url?scp=33746896140&partnerID=8YFLogxK

U2 - 10.1007/s10549-006-9207-y

DO - 10.1007/s10549-006-9207-y

M3 - Article

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AN - SCOPUS:33746896140

SN - 0167-6806

VL - 99

SP - 295

EP - 300

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -

Duration of letrozole treatment and outcomes in the placebo-controlled NCIC CTG MA.17 extended adjuvant therapy trial

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